1. Field of the Invention
The present invention relates to a short hairpin RNA, and a medicament comprising the hairpin RNA, particularly to a hairpin RNA targeting to NR1 subunit of N-methyl-D-aspartate receptor, and an analgesic drug with the above hairpin RNA.
2. Description of the Related Art
In general, pain induced by skin injuries, like burn or scald, is very complex and intolerable. Serious skin injuries usually cause an extensive release of peripheral neurotransmitter for activating glutamate receptors, including N-methyl-D-asparate (NMDA), α-amino-3-hydroxy-5-methylisoxazolone-4-propionic acid (AMPA) and kainite variants, which will turn on the mechanism of inflammatory pain and bring miserable pain to patients.
The NMDA receptors take important role in the central nervous system, and have been reported to involve in normal functions of central sensitization. Current reports suggest that the NMDA receptors located at sensory axons, as well as the general functions thereof, can be attenuated by localized delivery of a NMDA receptor antagonist. With such investment, the NMDA receptor antagonization provides an alternative approach of inflammatory pain treatment in clinical medicine.
With reference to Taiwan Patent Application No. 099107164, also known as U.S. patent application Ser. No. 12/780,278 and entitled with “A SMALL INTERFERING RNA FOR GENE KNOCKDOWN OF THE SUBCUTANEOUS N-METHYL-D-ASPARTATE RECEPTOR NR1 SUBUNIT AND ITS APPLICATION ON PHARMACEUTICS”, a small interfering RNA (siRNA) is synthesized and applied to clinical treatment of inflammatory pain. By subcutaneous injection of the siRNA, neither the mRNA, nor the protein of the NR1 subunit of NMDA receptors can normally express. As a result, the inflammatory pain on skin-injured patients will be effectively relieved.
However, siRNAs have unstable double-stranded structure, being easily and rapidly degradable after delivery into living organisms. The limitation of the synthetic siRNAs-mediated RNA interference (RNAi) in cells is that it is a transient effect, with the cells rapidly recovering from a single treatment. It emerges that the siRNAs of the conventional invention is limited to achieve long-term gene silencing and a long-period of analgesia. Hence, an alternative approach is needed for improving the shortage of the siRNAs of the conventional invention, and providing long-term gene silencing and antinociception.